OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
Mice ; Animals ; Mitogen-Activated Protein Kinase 14/metabolism* ; Wolfiporia ; Lipopolysaccharides/pharmacology* ; Sepsis/complications* ; Signal Transduction ; Inflammation/drug therapy* ; Oxygen Radioisotopes

Objective To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears.Methods From January 2019 to June 2022,22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique,including 10 males and 12 females,aged from 46 to 76 years old with an average of(64.14±7.45)years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42)months;19 patients were complete repaired,and 3 patients were partial repaired.Visual analogue scale(VAS)and University of California at Los Angeles(UCLA)scale were used to evaluate pain and function of shoulder joint preopera-tively and 1 year postoperatively.Postoperative complications,the integrity of reconstructed tissue structure and the size of sub-acromial space were observed.Results All patients were followed up from 12 to 34 months with an average of(17.14±5.93)months.Re-tear were occurred in 4 patients during MRI follow-up,but clinical symptoms of patients were improved significant-ly and they were satisfied with the treatment,the others were no complications such as incision infection,peripheral nerve in-jury,loosening and falling off of internal fixation anchors.Preoperative and 1 year after operation VAS were(8.05±1.12)and(1.82±1.50),UCLA scores were(7.45±1.65)and(31.41±2.87)respectively,and the difference was statistically significant(P＜0.05).Conclusion The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well,with satisfactory curative effect.

Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Ursodeoxycholic Acid/adverse effects* ; Berberine/pharmacology* ; Interleukin-6 ; Tumor Necrosis Factor-alpha/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Colon ; Nanoparticles ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Colitis/chemically induced*

OBJECTIVE To observe the changes in brain function characteristics of Chaihu Tongbian Decoction in rats with slow transit constipation(STC)and depression using resting-state functional magnetic resonance imaging(rs-fMRI).METHODS 70 healthy SPF grade male SD rats were randomly divided into the blank group,model group,mosapride group,fluoxetine hydrochloride group,low(11.02 g·kg-1),medium(22.05 g·kg-1),and high(44.1 g·kg-1)dose Chaihu Tongbian Decoction groups.A rat model of STC with depression was constructed using compound diphenylephrine tablets combined with solitary confinement and chronic unpredictable mild stress(CUMS).Drugs were administered after successful modeling.The general condition of the rats was observed;24 h total number of fecal particles,fecal water content and intestinal carbon end advance rate were calculated;HE staining of the co-lon tissue was performed;the depressive-like behavior of the rats was detected.By comparing rs-fMRI amplitude of low-frequency fluctuation(ALFF)values,the differences in neuronal activity in the brains of rats in each group were explored.RESULTS Com-pared with the blank group,the 24 h total number of fecal particles,fecal water content and intestinal carbon end advance rate in the model group were significantly reduced(P<0.01).HE staining showed that the colon tissue lesions in the model group were severe.Open field experiment and sugar water consumption showed that the activity level of rats in the model group decreased(P<0.01),and behavioral changes like anxiety and depression appeared.The rs-fMRI results showed that compared with the blank group,the ALFF value of the right posterolateral hippocampus in the model group decreased and the ALFF value of the left amygdala increased(P<0.01).Compared with the model group,after 4 weeks of treatment,the 24 h total number of fecal particles,fecal water content,and intestinal carbon end advance rate in the mosapride group and each dose group of Chaihu Tongbian Decoction were im-proved(P<0.05);compared with the model group,after 4 weeks of treatment,the fluoxetine hydrochloride group and each dose group of Chaihu Tongbian Decoction could improve the anxiety and depression-like behavior of rats(P<0.05);compared with the model group,after 4 weeks of treatment,the fluoxetine hydrochloride group and the high-dose Chaihu Tongbian Decoction group could in-crease the ALFF value of the right posterolateral hippocampus and decrease the ALFF value of the left amygdala(P<0.05).CON-CLUSION Chaihu Tongbian Decoction can effectively relieve constipation and depressive symptoms in STC rats with depression,and its mechanism may be related to activating the right posterolateral hippocampus and inhibiting amygdala activity.

ObjectiveTo establish blood stasis models in zebrafish using three inducers and select the optimal model for evaluating the activity of Notoginseng Radix et Rhizoma in promoting blood circulation. MethodArachidonic acid （AA）， ponatinib， and isoprenaline （ISO） were used to induce blood stasis models in zebrafish. A normal group， a model group， a positive drug group， and Notoginseng Radix et Rhizoma water extract freeze-dried powder groups at different concentrations were set up. The staining intensity of cardiac erythrocytes and the fluorescence intensity of cardiac apoptotic cells were calculated， the anti-thrombotic effect and anti-myocardial hypoxia activity of Notoginseng Radix et Rhizoma were evaluated. The activities of water extract and 70% methanol extract of Notoginseng Radix et Rhizoma were compared based on the preferred AA- and ISO-induced blood stasis models in zebrafish and the difference in the chemical composition was analyzed by UHPLC LTQ-Orbitrap MS/MS. ResultAfter induction by AA and ponatinib， the staining intensity of cardiac erythrocytes was reduced （P<0.01）， and the fluorescence intensity of cardiac apoptotic cells increased after the induction by ISO （P<0.01）. The freeze-dried powder of the water extract of Notoginseng Radix et Rhizoma could antagonize the thrombosis in the AA-induced model （P<0.01） and the myocardial apoptosis in the ISO-induced model （P<0.05）， while no significant improvement in the thrombosis was observed in the ponatinib-induced model. The freeze-dried powder of 70% methanol extract of Notoginseng Radix et Rhizoma could inhibit myocardial apoptosis in the ISO-induced blood stasis model （P<0.01）， and the effect was stronger than that of the freeze-dried powder of Notoginseng Radix et Rhizoma water extract. The difference in chemical composition lay in some saponins （such as ginsenoside Re）， amino acids， and acetylenic alcohols. ConclusionAA， ponatinib， and ISO all can serve as inducers for the blood stasis model in zebrafish. AA- and ISO-induced models can be used to evaluate the activity of freeze-dried powder of Notoginseng Radix et Rhizoma water extract in promoting blood circulation. The chemical compositions of the freeze-dried powders of Notoginseng Radix et Rhizoma extracted with water and 70% methanol are quite different. For the ISO-induced blood stasis model， the freeze-dried powder of Notoginseng Radix et Rhizoma extracted with 70% methanol has a stronger ability against myocardial hypoxia. Saponins and acetylenic alcohols may be closely related to the effects of promoting blood circulation and resolving blood stasis.

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

BACKGROUND: The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes. METHODS: A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs). RESULTS: The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88-40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001). CONCLUSIONS These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.
Cerebrovascular Disorders/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Proportional Hazards Models ; Retrospective Studies ; Transplantation Conditioning ; Transplantation, Autologous